The Stress Process Model predicts that caregivers should have higher rates of health decline than non-caregivers because of their higher stress levels. However, recent studies have found lower rates of mortality, frailty, and physical and cognitive functioning in older caregivers than non-caregivers. The proposed study will investigate four possible mechanisms for these better health outcomes: inflammatory burden as a psycho-neuroimmunological mechanism;the Healthy Caregiver Hypothesis, as a basic health advantage in older adults who become caregivers and continue caregiving;positive affect as a general psychological protective effect;and personal gain from caregiving as a caregiving-specific mechanism. This revised proposal is a competitive renewal of Caregiver-SOF, which is an ancillary study to the Study of Osteoporotic Fractures (SOF), a multi-site cohort study of elderly women. The Caregiver-SOF sample includes 1069 SOF participants: 375 caregivers and 694 non-caregivers matched on SOF site, age, race, and zip code. Caregiver-SOF participants have been followed since 1999 through 5 home-based interviews (3 annual interviews followed by 2 at 18-month intervals) that included standardized questions on caregiving and caregiver status transitions, perceived stress, physical and psychological health status;performance- based measures of physical functioning (timed walk, grip strength, chair stands) and cognitive functioning (Digit Substitution Test and Hopkins Verbal Learning Test). The proposed study will link to SOF to update mortality data, test the Healthy Caregiver Hypothesis, and use stored serum from SOF visits 8 and 9 for assays on 3 inflammatory markers (Interleukin-6, IL-6;C-reactive protein, CRP;and Tumor Necrosis Factor- alpha, TNF-1). We will use mixed longitudinal models and Cox proportional hazards models to test four hypotheses in all participants and in caregivers only. H1) Higher inflammatory burden (a summary score of IL-6, CRP, and TNF- 1 levels) will mediate associations between caregiving, including high-stress caregiver subgroups (e.g., dementia caregivers), and adverse health outcomes (i.e., mortality, decline in physical functioning, cognitive functioning). H2) SOF participants who were caregivers at both screening interviews for the Caregiver-SOF study, or who became caregivers at the second screening interview, will have better health status and less health decline than those who remained as non-caregivers or stopped caregiving. H3) Respondents with high positive affect, based on the positive affect subscale of the CES-D scale, will have less adverse health outcomes than other respondents;caregivers with high positive affect will be more likely to continue caregiving and adapt to cessation of caregiving. H4) Caregivers with more personal gain from caregiving will be more likely to continue caregiving, have lower inflammatory burden, and fewer adverse health outcomes. This study will provide important insights into associations between caregiving and health decline and will guide interventions to promote physical and cognitive health in older caregivers. PUBLIC HEALTH RELEVANCE: Recent studies have found lower rates of mortality, frailty, and physical and cognitive functioning in older caregivers compared to non-caregivers. The proposed study will use data collected over 10 years among 1069 older women caregivers and non-caregivers from the Caregiver-Study of Osteoporotic Fractures (Caregiver-SOF) cohort to investigate four possible reasons for these better health outcomes: lower systemic inflammation, better health constitutions in caregivers than non-caregivers, greater positive affect, and greater personal gain from caregiving. The results will advance our knowledge of the relationship between caregiving and health, and will have implications for designing interventions to promote physical and cognitive health in older caregivers.